Intrauterine contraceptive method

ABSTRACT

A method of contraception is disclosed characterized by providing for the presence of elemental copper or zinc in the uterine cavity. This invention is preferably practiced by wrapping a small amount of wire or foil or by placing a sleeve around a conventional intrauterine device prior to implantation. In a modification of this method, two different metals are employed to provide improved effectiveness.

United States Patent inventor Jaime A. Zipper Santiago, Chile Sept. 18,1968 Feb. 16, 1971 By mesne assignments, to G. D. Searle & Co. Chicago,Ill.

Appl. No. Filed Patented Assignee INTRAUTERINE CONTRACEPTIVE METHOD 8Claims, No Drawings References Cited UNITED STATES PATENTS PrimaryExaminer-Adele M. Eager Attorney-Curtis, Morris & Safford ABSTRACT: Amethod of contraception is disclosed characterized by providing for thepresence of elemental copper or zinc in the uterine cavity. Thisinvention is preferably practiced by wrapping a small amount of wire orfoil or by placing a sleeve around a conventional intrauterine deviceprior to implantation. In a modification of this method, two differentmetals are employed to provide improved effectiveness.

INTRAUTERINE CONTRACEPTIVE METHOD This invention relates to an improvedcontraceptive method.

During recent past years, due to world population pressures, a vastamount of research has been undertaken directed to developing improvedcontraceptive methods. One such method which has gained wide favorbecause of its high effectiveness is to employ certain hormones known tomodify the body endocrinology and suppress ovulation. These hormones,popularly administered as birth control pills, if used regularly, proveto be highly effective and reliable for controlling conception.Nevertheless, they are not without difficulties when used in large scalebirth control programs in developed and in developing countries, notonly because they are relatively expensive, but also becauseconsiderable reliance has to be placed upon the patient to take thepills in accordance-with the prescribed regimen.

In view of these disadvantages of conventional control pills, use ofintrauterine contraceptive devices has achieved considerable popularity.Such devices may be inserted inexpensively in patients in large scaleprograms, and moreover, do not require reliance upon a patientsswillingness or ability to follow a particular regimen of treatment.Despite these advantages of the intrauterine contraceptive devices whichare already available and being manufactured commercially, it has beenbeen found that they are not as effective as the socalled conventionalbirth control pills, provided the latter are used within the prescribedregimen. Accordingly, considerable effort has been directed towardimproving the efficacy of intrauterine contraceptive devices.

In accordance with the present invention, it has been found that thepresence of elemental copper of zinc in the uterine cavity is highlyeffective to prevent conception.

The elemental metal may be inserted or implanted in the uterine cavityby any convenient method. Normally, only a relatively small amount isrequired, for example, a small piece of copper or zinc wire in the orderof l to 2 centimeters in length and a fraction of a millimeter indiameter is effective. The effectiveness of a given quantity of metalappears to be related to the exposed surface area. In general it isbelieved that an exposed metallic surface of at least about 20 squaremillimeters is sufficient. Larger amounts may be used so long as thesize of the insert is not unacceptable.

' to 65 percent copper; copper-silver alloys containing up to 90 percentsilver; and copper-tin containing alloys such as certain admiraltymetals and bronzes (which may also contain other alloying elements suchas zinc, phosphorus, aluminum, manganese, etc.

A modification of the present invention which has been found to improveeffectiveness of the copper or zinc is to provide for the presence of asecond dissimilar metal. The second metallic element appears to have asynergistic effect on the copper or zinc since bimetallic couples areeven more effective as contraceptives. Any combination of a variety ofpharmaceutically acceptable metals or alloys thereof may be used; forexample, silver, stainless steel, gold, platinum, tin, brass, bronze,and the like. it will be obvious, moreover, that the combination ofcopper and zinc themselves can be used as a twometal system forimproving the efficacy of the present invention.

The present invention may be further understood by reference to thefollowing examples:

EXAMPLE 1 Comparative tests were performed on a group of patients toascertain the relative effectiveness under clinical conditions of thepresence of'a small amount of copper in the form of wire carried on anintrauterine device. A T-shaped plastic intrauterine device was placedin 250 members of the group as a control. In the control group noexogenous copper, zinc or other free elemental metal was present on theintrauterine device. In the balance of the group the same intrauterine 1device was used modified by winding; a piece of copper wire, 3

centimeters in length and millimeters in diameter, around V RESULTS OFIMPLANTATION OF INTRAUTERINE DEVICES PER 100 USERS Small quantities offoreign material in the uterine cavity,

however, would not ordinarily have the desired longevity of actionbecause they would be quickly expelled or sloughed off either throughmuscular uterine contractions or during the period of regular menstrualflow. Preferably, therefore, the elemental metal in implanted wit withinthe uterine cavity by means of a carrier, for which purpose any of theconventional intrauterine contraceptive devices are eminently suitable.A

wide variety of such devices are known, i.e., single or multiple loops,spirals, crosses, and various sinuous shapes. The metal may be depositedonto the carrier in the following manners: (a) it could be in the formof wire which would be wound around a portion of the carrier; (b) themetal could be in the form of foil and could be wrapped around thecarrier; (c) the metal could be in the form of tubing and could heslipped onto a portion of the carrier as a sleeve and swaged in place bypressure; (d) the metal could be applied to the carrier by means of aplating process; (e) metal filings, powder, etc. may be intimatelyblended with the resinous material from which the intrauterine device ismade.

The contraceptive properties of metallic copper were determined inexperimental animals in the following manner:

served as the site of the intrauterine device.

Under general anesthesia an abdominal incision was made and a l.5 cm.length of wire consisting of four strands of wire each of which was 0.15mm. in diameter was inserted in the lower portion of the cavity of theright uterine horn close to the cervical os. The wire was fastened inplace by a silk suture through the myometrium in order to avoidexpulsion. The left horn remained intact.

After a week of rest the rabbits were mated. Ten days after mating, theoccurence of pregnancy was determined by obf serving the implantationsites through an abdominal incision.

There were no implantations in the right uterine horn which containedthe copper wire. There were, however, an average Adult virgirial rabbitswere used. lln each instance, thele ft uterine horn served as thecontrol and the right uterine horn of 4.1 implantations per rabbit inthe left uterine horn which had remained intact. This exampleillustrates clearly and definitely that copper serves as a potentantifertility agent when it lies in the endometrial cavity.

EXAMPLE 3 The contraceptive properties of metallic zinc were determinedin experimental animals in the following manner:

Adult virginal rabbits were used. In each instance, the left uterinehorn served as the control and the right uterine horn served as the siteof the intrauterine device.

Under general anesthesia an abdominal incision was made and a 1.5 cm.length of zinc wire of 0.5 mm. diameter was inserted in the lowerportion of the cavity of the right uterine horn close to the cervical s.The wire was fastened in place by a silk suture through the myometriumin order to avoid expulsion. The left horn remained intact.

After a week of rest the rabbits were mated. Ten days after mating, theoccurence of pregnancy was determined by observing the implantationsites through an abdominal incision. There were no implantations in theright uterine hornwhich contained the zinc wire. There were, however, anaverage of 3.5 implantations per rabbit in the left uterine horn whichhad remained intact. This example illustrates clearly and definitelythat zinc serves as a potent antifertility agent when it lies in theendometrial cavity.

EXAMPLE 4 In order to illustrate the contraceptive properties of copperare related to the amount of surface are of the copper which is exposedwithin the uterine cavity, the following experiment was performed.

Adult virginal rabbits were divided into two groups. Under generalanesthesia and by the same surgical technique described in Examples 2and 3, a single 1.5 cm. length of copper wire 0.20 mm. in diameter wasaffixed within the right uterine horn of the animals in Group A, Thesame procedure was followed in Group B except that four 1.5 cm. segmentsof copper wire 0.20 mm. in diameter were wound together and were affixedwithin the right uterine horn. The left uterine horns of all animals inboth Groups A and B were kept intact and served as controls.

After a week of rest the rabbits were mated. Ten days after mating, theoccurence of pregnancy was determined by observing the implantationsites through an abdominal incision. There were no implantations in theright horns of the animals in Group B. There was no evidence of reducedimplantation in the right or in the left horn of the animals in Group A.This example clearly illustrates that the contraceptive properties ofcopper are determined to some degree by the surface area of copper whichis exposed within the uterine cavity.

EXAMPLE 5 The effectiveness of a twometal system was studied byimplantation of copper and silver couples in the rabbit uterus. Thestudy was performed as follows:

Adult virginal rabbits were divided in four groups. Under generalanesthesia the following foreign bodies were inserted in the lowerportion of the cavity of the right uterine horn close to the cervical05. These were fastened in place by a silk suture through the myometriumin order to avoid expulsion. In all four groups the left uterine hornwas kept intact and thus served as the control. The foreign body affixedwithin the right uterine horn in the four groups was as follows:

Group A-a single copper wire 0,20 mm. diameter and 1.5

cm. long; Group B-a single copper wire 0.20 mm. diameter and 1.5 cm.long wound around a silver wire 0.35 mm. diameter and 1.5 cm. long;

Group C-a silver wire 0.35 mm. diameter and 1.5 cm. long; Group D-fourcopper wires 0.20 mm. diameter and 1.5 cm.

long.

After a week of rest the rabbits were mated. Ten days after mating, theoccurence of pregnancy was determined by observing the implantationsites through an abdominal incision. In group A it was found that thepresence of a single copper wire 0.20 mm. in diameter and 1.5 cm. longdid not produce a marked effect on implantation rates in either theright uterine horn where the wire was implanted or in the contralateralhorn. On the other hand, the presence of the two metals, i.e., Group B,with the same quantity of copper as in Group A, showed a remarkabledecrease in the number of implantations in the right uterine horn wherethe two wires were placed. lmplantations were normal in thecontralateral horn. The silver wire used in Group C did not produce aneffect on implantation rates. When the amount of copper was increased inGroup D, no implantations were observed in the right uterine horn wherethe wires were placed. Implantations were normal in the contralateralhorn. This example clearly illustrates that when two metals aremechanically combined and inserted in the uterine cavity, thecontraceptive properties are greater than then when one or the othermetal is used alone.

I claim:

1. A method of contraception which comprises placing a contraceptivelyeffective amount of an elemental metal selected from the groupconsisting of copper and zinc in the uterine cavity.

2. A method as in claim 1 wherein a said elemental metal is attached toan intrauterine device effective to retain said metal in the uterinecavity over a prolonged period of time.

3. A method as in claim 1 wherein said metal in is in the form of apharmaceutically acceptable alloy.

4. A method as in claim 1 wherein two dissimilar pharmaceuticallyacceptable metals are placed in the uterine cavity in contact with eachother, at least one of said metals being selected from the groupconsisting of copper and zinc.

5. A method as in claim 4 wherein said dissimilar metals are silver andcopper.

6. A method as in claim 1 wherein said elemental metal has an exposedsurface area of at least about 20 square millimeters.

7. An intrauterine contraceptive device adaptable to insertion in theuterine cavity and capable of being retained therein for prolongedperiods of time, said device including a contraceptively effectiveamount of an elemental metal selected from the group consisting ofcopper and zinc.

8. An intrauterine contraceptive device as in claim 7 wherein saidelemental metal has an exposed surface area of at least about 20 squaremillimeters.

2. A method as in claim 1 wherein a said elemental metal is attached toan intrauterine device effective to retain said metal in the uterinecavity over a prolonged period of time.
 3. A method as in claim 1wherein said metal in is in the form of a pharmaceutically acceptablealloy.
 4. A method as in claim 1 wherein two dissimilar pharmaceuticallyacceptable metals are placed in the uterine cavity in contact with eachother, at least one of said metals being selected from the groupconsisting of copper and zinc.
 5. A method as in claim 4 wherein saiddissimilar metals are silver and copper.
 6. A method as in claim 1wherein said elemental metal has an exposed surface area of at leastabout 20 square millimeters.
 7. An intrauterine contraceptive deviceadaptable to insertion in the uterine cavity and capable of beingretained therein for prolonged periods of time, said device including acontraceptively effective amount of an elemental metal selected from thegroup consisting of copper and zinc.
 8. An intrauterine contraceptivedevice as in claim 7 wherein said elemental metal has an exposed surfacearea of at least about 20 square millimeters.